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Zoological Research Sep 2023Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction. However, action recognition...
Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and prediction. However, action recognition currently used in non-human primate (NHP) research relies heavily on intense manual labor and lacks standardized assessment. In this work, we established two standard benchmark datasets of NHPs in the laboratory: MonkeyinLab (MiL), which includes 13 categories of actions and postures, and MiL2D, which includes sequences of two-dimensional (2D) skeleton features. Furthermore, based on recent methodological advances in deep learning and skeleton visualization, we introduced the MonkeyMonitorKit (MonKit) toolbox for automatic action recognition, posture estimation, and identification of fine motor activity in monkeys. Using the datasets and MonKit, we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the gene as a disease model of Rett syndrome (RTT). MonKit was used to assess motor function, stereotyped behaviors, and depressive phenotypes, with the outcomes compared with human manual detection. MonKit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency, thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.
Topics: Animals; Deep Learning; Macaca fascicularis; Skeleton; Mutation; Phenotype
PubMed: 37721106
DOI: 10.24272/j.issn.2095-8137.2022.449 -
PloS One 2023Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing...
Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children ("primary" stereotypies, pCMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with pCMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. Exploratory gene ontology and network analyses highlight functional convergence in calcium ion transport, demethylation, cell signaling, cell cycle and development. Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries.
Topics: Humans; Autism Spectrum Disorder; Tourette Syndrome; DNA; Exome Sequencing; Mutation; Genetic Predisposition to Disease; Nuclear Proteins; Repressor Proteins; Jumonji Domain-Containing Histone Demethylases
PubMed: 37788244
DOI: 10.1371/journal.pone.0291978 -
Science Advances Sep 2023Biological systems are inherently noisy; however, they produce highly stereotyped tissue morphology. pupal wings show a highly stereotypic folding through uniform...
Biological systems are inherently noisy; however, they produce highly stereotyped tissue morphology. pupal wings show a highly stereotypic folding through uniform expansion and subsequent buckling of wing epithelium within a surrounding cuticle sac. The folding pattern produced by buckling is generally stochastic; it is thus unclear how buckling leads to stereotypic tissue folding of the wings. We found that the extracellular matrix (ECM) protein, Dumpy, guides the position and direction of buckling-induced folds. Dumpy anchors the wing epithelium to the overlying cuticle at specific tissue positions. Tissue-wide alterations of Dumpy deposition and degradation yielded different buckling patterns. In summary, we propose that spatiotemporal ECM remodeling shapes stereotyped tissue folding through dynamic interactions between the epithelium and its external structures.
Topics: Animals; Extracellular Matrix; Epithelium; Extracellular Matrix Proteins; Drosophila; Stereotyped Behavior
PubMed: 37656799
DOI: 10.1126/sciadv.adh2154 -
Comprehensive Psychoneuroendocrinology Nov 2023Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by stereotyped behavior, restricted interests and social/communicative deficits. The...
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by stereotyped behavior, restricted interests and social/communicative deficits. The physiological etiology of ASD is not currently understood, however recent research has implicated dysregulation of the immune system as a central feature. The interplay between the stress systems, the immune system and the brain has been well-documented and implicated in other psychiatric and neurological disorders. This interplay suggests a role for the hypothalamic-pituitary-adrenal (HPA) axis in the etiology of ASD. We assessed levels of urinary cortisol and neopterin as markers of immune function and HPA activation in a cohort of 50 children from the central Johannesburg region. Additionally, we used the Autism Treatment Evaluation Checklist to assess autistic symptomatology and the Bruininks-Oseretsky Motor Proficiency Test (Second Edition) (BOT-2) to assess motor skills. No relationships were found between cortisol and autistic symptomatology. No relationships were found between neopterin and any of the other measures. However, a relationship was observed between urinary cortisol and performance on balance-related tasks from the BOT-2 (P < 0.05). Our findings support a theory of neurological interconnectedness between postural modulation and activation of the stress system, which has not previously been documented in children with ASD.
PubMed: 38023738
DOI: 10.1016/j.cpnec.2023.100216 -
Developmental Science Jul 2023How do gender stereotypes shape prototypes across development? In the current pre-registered study with children ages 3- to 10-years-old and adults (N = 257),...
How do gender stereotypes shape prototypes across development? In the current pre-registered study with children ages 3- to 10-years-old and adults (N = 257), participants made judgements about which members of gender categories (boys and girls) and animal categories (for comparison) were the most representative and informative about their kinds, using simplified scales of five category members varying on a stereotypical feature (e.g., girls wearing more or less pink). Young children chose boys and girls with extreme stereotypical features (e.g., the girl in head-to-toe pink) as both representative and informative of their categories and this tendency declined with age, similar to developmental patterns in prototypes of animal categories. Controlling for age, children whose parents reported more conservative social-political views also held more extreme gender (but not animal) prototypes. Thus, stereotypes play a central role in children's gender prototypes, especially young children and those living in socially-conservative households. A video abstract of this article can be viewed at https://youtu.be/Ps9BwuukyD0 RESEARCH HIGHLIGHTS: Stereotypes play a central role in children's gender prototypes, especially young children and those in socially-conservative households. Children ages 3-10 and adults chose which girls, boys, and animals were most representative and informative. Younger children chose category members with more extreme stereotypical features (e.g., the girl in head-to-toe pink) than older children and adults. Children with more conservative parents also held more extreme gender prototypes.
Topics: Child; Humans; Child Development; Parents; Judgment; Stereotyped Behavior; Family Characteristics
PubMed: 36374626
DOI: 10.1111/desc.13345 -
Biological Psychiatry. Cognitive... Apr 2024Impairing repetitive behaviors are one of the core diagnostic symptoms in autism spectrum disorder and obsessive-compulsive disorder, but they also manifest in...
BACKGROUND
Impairing repetitive behaviors are one of the core diagnostic symptoms in autism spectrum disorder and obsessive-compulsive disorder, but they also manifest in attention-deficit/hyperactivity disorder. Although the dorsal striatal circuit has been implicated in repetitive behaviors, extensive heterogeneity in and cross-diagnostic manifestations of these behaviors have suggested phenotypic and likely neurobiological heterogeneity across neurodevelopmental disorders (NDDs).
METHODS
Intrinsic dorsal striatal functional connectivity was examined in 3 NDDs (autism spectrum disorder, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder) and typically developing control participants in a large single-cohort sample (N = 412). To learn how diagnostic labels and overlapping behaviors manifest in dorsal striatal functional connectivity measured with functional magnetic resonance imaging, the main and interaction effects of diagnosis and behavior were examined in 8 models (2 seed functional connectivity [caudate and putamen] × 4 sub-behavioral domains [sameness/ritualistic, self-injury, stereotypy, and compulsions]).
RESULTS
The obsessive-compulsive disorder group demonstrated distinctive patterns in visual and visuomotor coordination regions compared with the other diagnostic groups. Lower-order repetitive behaviors (self-injury and stereotypy) manifesting across all participants were implicated in regions involved in motor and cognitive control, although the findings did not survive effects of multiple comparisons, suggesting heterogeneity in these behavioral domains. An interaction between self-injurious behavior and an attention-deficit/hyperactivity disorder diagnosis were observed on caudate-cerebellum functional connectivity.
CONCLUSIONS
These findings confirmed high heterogeneity and overlapping behavioral manifestations in NDDs and their complex underlying neural mechanisms. A call for diagnosis-free symptom measures that can capture not only observable symptoms and severity across NDDs but also the underlying functions and motivations of such behaviors across diagnoses is needed.
Topics: Child; Humans; Adolescent; Brain Mapping; Autism Spectrum Disorder; Cognition; Obsessive-Compulsive Disorder; Neurodevelopmental Disorders
PubMed: 38000717
DOI: 10.1016/j.bpsc.2023.10.014 -
Behavior Modification May 2024Complex motor stereotypies are rhythmic, repetitive, fixed, and non-goal directed movements (e.g., bilateral flapping/waving movements of the hands/arms). Movements...
Complex motor stereotypies are rhythmic, repetitive, fixed, and non-goal directed movements (e.g., bilateral flapping/waving movements of the hands/arms). Movements typically begin in early childhood and can occur in otherwise normally developing ("primary") or autistic ("secondary") children. Stereotypies persist, occur multiple times a day, have prolonged durations, can be socially stigmatizing, and may lead to bullying and isolation. Prior behavioral treatment studies have focused on older children (ages 6-12) and report modest reductions in stereotypy (i.e., between 14% and 33%). The current study involves the functional assessment and treatment of five children with Primary Complex Motor Stereotypy using a modified awareness training procedure, differential reinforcement of other behavior, and schedule thinning in a nonconcurrent multiple baseline design. Results suggest a 99% reduction of motor stereotypy from baseline across all participants.
PubMed: 38819977
DOI: 10.1177/01454455241255085 -
The Journal of Neuroscience : the... Oct 2023Social touch, an important aspect of social interaction and communication, is essential to kinship across animal species. How animals experience and respond to social...
Social touch, an important aspect of social interaction and communication, is essential to kinship across animal species. How animals experience and respond to social touch has not been thoroughly investigated, in part because of the lack of appropriate assays. Previous studies that examined social touch in freely moving rodents lacked the necessary temporal and spatial control over individual touch interactions. We designed a novel head-fixed assay for social touch in mice, in which the experimenter has complete control to elicit highly stereotyped bouts of social touch between two animals. The user determines the number, duration, context, and type of social touch interactions, while monitoring an array of complex behavioral responses with high resolution cameras. We focused on social touch to the face because of its high translational relevance to humans. We validated this assay in two different models of autism spectrum disorder (ASD), the knock-out (KO) model of Fragile X syndrome (FXS) and maternal immune activation (MIA) mice. We observed higher rates of avoidance running, hyperarousal, and aversive facial expressions (AFEs) to social touch than to object touch, in both ASD models compared with controls. KO mice showed more AFEs to mice of the same sex but whether they were stranger or familiar mice mattered less. Because this new social touch assay for head-fixed mice can be used to record neural activity during repeated bouts of social touch it could be used to uncover underlying circuit differences. Social touch is important for communication in animals and humans. However, it has not been extensively studied and current assays to measure animals' responses to social touch have limitations. We present a novel head-fixed assay to quantify how mice respond to social facial touch with another mouse. We validated this assay in autism mouse models since autistic individuals exhibit differences in social interaction and touch sensitivity. We find that mouse models of autism exhibit more avoidance, hyperarousal, and aversive facial expressions (AFEs) to social touch compared with controls. Thus, this novel assay can be used to investigate behavioral responses to social touch and the underlying brain mechanisms in rodent models of neurodevelopmental conditions, and to evaluate therapeutic responses in preclinical studies.
Topics: Humans; Mice; Animals; Autistic Disorder; Touch; Autism Spectrum Disorder; Fragile X Mental Retardation Protein; Fragile X Syndrome; Mice, Knockout; Disease Models, Animal
PubMed: 37669860
DOI: 10.1523/JNEUROSCI.0226-23.2023 -
European Journal of Clinical... Oct 2023The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children. (Meta-Analysis)
Meta-Analysis
PURPOSE
The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children.
METHODS
A systematic literature search was conducted to identify randomized controlled trials (RCTs) of oxytocin for the treatment of core symptoms in children with ASD. The search included studies published between January 1, 1999 and March 15, 2023, that were randomized, single or double-blinded, and included a placebo control group. Standard screening rules were applied to select relevant studies, resulting in the inclusion of five RCTs involving 486 children with ASD.
RESULTS
Ultimately, a total of five RCTs, involving 486 children with ASD, were included in the review using standard screening rules.One of the included studies demonstrated a statistically significant improvement in Social Responsiveness Scale (SRS) and Repetitive Behavior Scale-Revised (RBS) scores when children with ASD were treated with oxytocin (24 IU/2 days for 6 weeks). The improvement in core symptoms persisted at the 6-month follow-up. The meta-analysis findings suggested that oxytocin might have a moderate effect in improving the core symptom of narrow interests and repetitive stereotyped behaviors in children with ASD.
CONCLUSION
While the therapeutic value of oxytocin in treating core symptoms of ASD in children is not fully established, the results of this meta-analysis indicate a potential moderate effect. However, further studies with larger sample sizes and more robust RCTs are needed to directly demonstrate the efficacy of oxytocin. Future research should also focus on effect size and outcome evaluation accuracy while minimizing bias in RCT experiments.
Topics: Humans; Child; Oxytocin; Autism Spectrum Disorder; Outcome Assessment, Health Care; Control Groups
PubMed: 37540265
DOI: 10.1007/s00228-023-03545-w -
PLoS Computational Biology Mar 2024Social reputations provide a powerful mechanism to stimulate human cooperation, but observing individual reputations can be cognitively costly. To ease this burden,...
Social reputations provide a powerful mechanism to stimulate human cooperation, but observing individual reputations can be cognitively costly. To ease this burden, people may rely on proxies such as stereotypes, or generalized reputations assigned to groups. Such stereotypes are less accurate than individual reputations, and so they could disrupt the positive feedback between altruistic behavior and social standing, undermining cooperation. How do stereotypes impact cooperation by indirect reciprocity? We develop a theoretical model of group-structured populations in which individuals are assigned either individual reputations based on their own actions or stereotyped reputations based on their groups' behavior. We find that using stereotypes can produce either more or less cooperation than using individual reputations, depending on how widely reputations are shared. Deleterious outcomes can arise when individuals adapt their propensity to stereotype. Stereotyping behavior can spread and can be difficult to displace, even when it compromises collective cooperation and even though it makes a population vulnerable to invasion by defectors. We discuss the implications of our results for the prevalence of stereotyping and for reputation-based cooperation in structured populations.
Topics: Humans; Cooperative Behavior; Models, Psychological; Altruism; Mass Behavior
PubMed: 38427626
DOI: 10.1371/journal.pcbi.1011862